Taxanes are one of the most important classes of anticancer drugs recently developed. The remarkable effectiveness of Paclitaxel and of its analogue Docetaxel in the treatment of several tumors has focused research on substances with antimicrotubular activity. Taxanes are however characterized by a particular action mechanism, in that they promote the assembly of microtubules and inhibit tubuline depolymerization.
The main drawbacks of the taxanes presently used are: (a) insolubility in water, making mandatory the use of specific carriers which can cause hypersensitization reactions, (b) toxicities which limit dosages, (c) development of resistance mechanisms. Cell resistance to taxanes has been related to the MDR phenotype (“multidrug resistance”) mediated by the P-glycoprotein transporter, by tubuline alterations, and by changes in the expression of apoptotic regulatory proteins.
In order to find novel active molecules having higher solubility and better tolerability, 14β-hydroxy-10-deacetylbaccatine III and V taxane derivatives have been synthesized.
Some derivatives of 14-hydroxy baccatine III substituted at the 13-position by isoserine residues are disclosed in U.S. Pat. No. 5,705,508, together with a process for the preparation thereof.